Receptors for the Fc portion of immunoglobulin G (IgG) play a central role in cellular immune defenses. Three types of such receptors have been identified: A 72 kilodalton (D) receptor with high affinity for monomeric IgG is found on monocytes and some macrophages, a 40 D receptor with low affinity for monomeric IgG is found on monocytes, neutrophils, eosinophils, platelets, and certain human tumor-cell lines, and a 50-70 D receptor with low affinity for monomeric IgG is found on neutrophils, eosinophils, natural killer cells, and macrophages. These three types of Fc.gamma. receptor are referred to as Fc.gamma.RI, Fc.gamma.RII, and Fc.gamma.RIII, respectively: Unkeless et al., Ann. Rev. Immunol., Vol. 6 , pgs. 251-281 (1988).
It is believed that Fc.gamma.RIII-mediated removal of IgG-coated platelets plays an important part in the pathogenesis of immune thrombocytopenic purpura (ITP), a platelet-deficiency condition characterized by excessive bleeding: von dem Borne, pgs. 222-256, in Immunohaematology, Engelfriet et al., eds. (Elsevier, Amsterdam, 1984). Clerkson et al., New England J. Med., Vol. 314,pgs. 1236-1239 (1986) , report that the infusion of ligand-blocking anti-Fc.gamma.RIII antibody into a patient with refractory ITP resulted in transient increase in platelet count. This observation suggests that the most deleterious manifestation of ITP could be temporarily ameliroated by the administration of agents that block or compete with Fc.gamma.RIII for binding sites on IgG-coated platelets.
In a separate area of clinical immunology, elevated serum levels of aggregates consisting of immunoglobulin and antigen (so-called "immune complexes") have been correlated with a wide variety of disorders, particularly autoimmune diseases, such as systemic lupus erythematosus (SLE), and rheumatoid arthritis. The level of such complexes has become an important diagnostic for presence of autoimmune disorder; e.g. Theofilopoulos et al., Am.J. Pathol., Col. 100, pgs. 531-591 (1980).
Present assays for the serum level of immune complexes include solid-phase assays which take advantage of the affinity of the complexes for certain complement or rheumatoid factor proteins, and cellular assays which take advantage of the property of Raji cells to preferentially bind immune complexes; Theofilopoulos et al., chapter 28, and Toth et al., chapter 29, in Rose et al., eds. Manual of Clinical Immunology, 3rd Ed. (American Society for Microbiology, Washington, D.C., 1986). Unfortunately, like many mammalian-cell based assays, the Raji-cell assay is difficult to perform, and requires elaborate controls and standards because of the inherent variability of Raji-cell binding to immune complexes.
In light of the foregoing, it would be advantageous for the medical community to have alternative assay methods for immune complexes utilizing well characterized, widely available, and conveniently cultured cell lines. It would also be advantageous if soluble Fc.gamma.Rs could be produced in sufficient quantity to permit practical emergency therapy for refractory cases of ITP.